[HTML][HTML] Interleukin-4 acts at the locus of the antigen-presenting dendritic cell to counter-regulate cytotoxic CD8+ T-cell responses

C King, R Mueller Hoenger, M Malo Cleary… - Nature medicine, 2001 - nature.com
C King, R Mueller Hoenger, M Malo Cleary, K Murali-Krishna, R Ahmed, E King…
Nature medicine, 2001nature.com
The mechanism underlying suppression of immune responses by interleukin-4 (IL-4) has
remained unexplained. Here we show that the antigen-presenting dendritic cell is central to
counter-regulation of autoimmune disease by IL-4. IL-4 acts at the locus of the dendritic cell
to decrease the cytolytic T-cell response, preventing autoimmunity. Stimulation of cytotoxic
precursors by antigen pulsed dendritic cells induces their differentiation but the process is
blocked by IL-4. IL-4-influenced DC produce distinct effects on CD8+ T cells depending on …
Abstract
The mechanism underlying suppression of immune responses by interleukin-4 (IL-4) has remained unexplained. Here we show that the antigen-presenting dendritic cell is central to counter-regulation of autoimmune disease by IL-4. IL-4 acts at the locus of the dendritic cell to decrease the cytolytic T-cell response, preventing autoimmunity. Stimulation of cytotoxic precursors by antigen pulsed dendritic cells induces their differentiation but the process is blocked by IL-4. IL-4-influenced DC produce distinct effects on CD8+ T cells depending on their state of activation. The molecular basis for this regulation is the alteration of the expression ratio of the costimulatory ligands B7. 1/B7. 2 on dendritic cells. Our findings demonstrate that B7. 2 induces expansion of CD8+ T cells and B7. 1 governs their acquisition of cytolytic activity. IL-4 influences the dendritic cell to elicit qualitative differences in T-cell responses, providing the basis for counter-regulation mediated by IL-4.
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